This application proposes to investigate the correlation of structure and function in the mammalian nephron. The basic mode of investigation will employ differential interference - contrast and fluorescence microscopy on living, isolated, perfused, proximal straight and cortical collecting tubules. A full range of physiologic measurements will be made with simultaneous closed-circuit video recording of structural features. The fundamental questions we are asking concern the transepithelial route of fluid absorption in the proximal nephron and the cellular response to antidiuretic hormone-induced hydroosmotic flow in the cortical collecting tubule. In proximal tubule studies we will examine the dependence of cell volume on the fluid absorption rate when the driving force is active solute transport and when only dissipative forces are operative as in the case of an established anion asymmetry. We also plan to investigate whether lateral intercellular spaces dilate significantly during fluid flow and the importance of peritubular concentrations of albumin. The collecting tubule will be examined with respect to structural changes, including cell swelling, vacuolation and intercellular space geometry. We plan to make extensive use of fluorochromes to examine mitochondrial shape and, through acidification, transcellular water pathways.